Person:
Cazorla Luna, Raúl

First Name

Raúl

Last Name

Cazorla Luna

URI

https://hdl.handle.net/20.500.14352/86943

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

Identifiers

Full item page

Search Results

Now showing 1 - 9 of 9

Dapivirine Bioadhesive Vaginal Tablets Based on Natural Polymers for the Prevention of Sexual Transmission of HIV
(Polymers, 2019) Cazorla Luna, Raúl; Martín Illana, Araceli; Notario Pérez, Fernando; Bedoya del Olmo, Luis Miguel; Ruiz Caro, Roberto; Bermejo Benito, Paulina; Veiga Ochoa, María Dolores
Young sub-Saharan women are a group that is vulnerable to the sexual transmission of HIV. Pre-exposure prophylaxis through vaginal microbicides could provide them an option for self-protection. Dapivirine has been demonstrated to have topical inhibitory effects in HIV, and to provide protection against the sexual transmission of this virus. This paper reports on the studies into swelling behaviour, bioadhesion and release carried out on dapivirine tablets based on chitosan, locust bean gum and pectin, to select the most suitable formulation. The modified simulated vaginal fluid led to a high solubility of dapivirine and allowed the dapivirine release profiles to be characterized in sink conditions; this aqueous medium is an alternative to organic solvents, which are not a realistic option when evaluating systems whose behaviour varies in aqueous and organic media. Of the formulations evaluated, dapivirine/pectin tablets containing 290 mg of polymer and 30 mg of dapivirine present the most moderate swelling, making them the most comfortable dosage forms. Their high bioadhesive capacity would also allow the formulation to remain in the action zone and release the drug in a sustained manner, pointing to this formulation as the most promising candidate for future evaluations of vaginal microbicides for the prevention of HIV.
Smart Freeze-Dried Bigels for the Prevention of the Sexual Transmission of HIV by Accelerating the Vaginal Release of Tenofovir during Intercourse
(Pharmaceutics, 2019) Martín Illana, Araceli; Notario Pérez, Fernando; Cazorla Luna, Raúl; Ruiz Caro, Roberto; Veiga Ochoa, María Dolores
Sub-Saharan African women are still at risk from the human immunodeficiency virus (HIV), and sex with men is the main route of transmission. Vaginal formulations containing antiretroviral drugs are promising tools to give women the power to protect themselves. The aim of this work was to obtain freeze-dried bigels containing pectin, chitosan, or hypromellose for the vaginal controlled release of Tenofovir, which is accelerated in the presence of semen. Nine batches of bigels were formulated using di_erent proportions of these polymers in the hydrogel (1, 2, and 3% w/w). The bigels obtained were freeze-dried and then underwent hardness and deformability, mucoadhesion, swelling, and drug release tests, the last two in simulated vaginal fluid (SVF) and SVF/simulated seminal fluid (SSF) mixture. The formulation containing 3% pectin (fd3P) has the highest values for hardness, resistance to deformation, and good mucoadhesivity. Its swelling is conditioned by the pH of the medium, which is responsive to the controlled release of Tenofovir in SVF, with the fastest release in the SVF/SSF mixture. fd3P would be an interesting smart microbicidal system to allow faster reléase of Tenofovir in the presence of semen, and thus increase women’s ability to protect themselves from the sexual transmission of HIV.
Mucoadhesive Vaginal Discs based on Cyclodextrin and Surfactants for the Controlled Release of Antiretroviral Drugs to Prevent the Sexual Transmission of HIV
(Pharmaceutics, 2020) Notario Pérez, Fernando; Martín Illana, Araceli; Cazorla Luna, Raúl; Ruiz Caro, Roberto; Tamayo, Aitana; Rubio, Juan; Veiga Ochoa, María Dolores
The strategies for developing vaginal microbicides to protect women against human immunodeficiency virus (HIV) sexual transmission are constantly changing. Although the initial dosage forms required daily administration to offer effective protection, the trend then moved towards sustained-release dosage forms that require less frequency of administration in order to improve women’s compliance with the treatment. Nevertheless, another possible strategy is to design on-demand products that can be used in a coitally-dependent manner and only need to be administered immediately before intercourse to offer protection. Vaginal discs based on freeze-dried hydroxypropylmethyl cellulose gels have been developed for this purpose, containing two surfactants, i.e., sodium dodecyl sulphate and polysorbate 60, alone or in combination with 2-hydroxypropyl-β cyclodextrin, to achieve a formulation capable of incorporating both hydrophilic and lipophilic drugs. Several studies have been carried out to evaluate how the inclusion of these substances modifies the structure of gels (viscosity and consistency studies) and the porosimetry of the freeze-dried discs (scanning electron microscopy micrographs, mechanical properties, swelling behaviour). The drug release and mucoadhesive properties of the discs have also been evaluated with a view to their clinical application. The systems combining sodium dodecyl sulphate and 2-hydroxypropyl-β-cyclodextrin were found to be adequate for the vaginal administration of both Tenofovir and Dapivirine and also offer excellent mucoadhesion to vaginal tissue; these discs could therefore be an interesting option for a coitally-dependent administration to protect women against HIV transmission.
Chitosan-Based Mucoadhesive Vaginal Tablets for Controlled Release of the Anti-HIV Drug Tenofovir
(Pharmaceutics, 2019) Cazorla Luna, Raúl; Notario Pérez, Fernando; Martín Illana, Araceli; Ruiz Caro, Roberto; Tamayo, Aitana; Rubio, Juan; Veiga Ochoa, María Dolores
Vaginal microbicides have the potential to give women at high risk of contracting HIV the option of self-protection by preventing the sexual transmission of the virus. In this paper, mucoadhesive vaginal tablets based on chitosan, alone and in combination with pectin and locust bean gum, were developed for the sustained release of tenofovir (an antiretroviral drug). The formulations were placed in simulant vaginal fluid (SVF) to swell, and Hg porosity and SEM microscopy were used for the microstructural characterization of the swelling witnesses. The results show that the association of pectin and chitosan generated polyelectrolyte complexes and produced a robust system able to maintain its structure during the swelling process, when small pores are formed. Drug reléase and bovine vaginal mucoadhesion studies were performed in SVF showing that tenofovir-controlled dissolution profiles and adhesion to the mucosa were conditioned by the swelling processes of the polymer/s in each formulation. Tablets based on chitosan/pectin have the most homogeneous tenofovir dissolution profiles and last up to 96 h, remaining attached to the vaginal mucosa for the same period. These formulations can therefore be considered a good option for the self-protection of women from the sexual transmission of HIV.
Tenofovir Hot-Melt Granulation using Gelucire® to Develop Sustained-Release Vaginal Systems for Weekly Protection against Sexual Transmission of HIV
(Pharmaceutics, 2019) Notario Pérez, Fernando; Cazorla Luna, Raúl; Martín Illana, Araceli; Ruiz Caro, Roberto; Peña López, Juan; Veiga Ochoa, María Dolores
Hot-melt granulation is a technique used to obtain granules by dispersing a drug in polymers at a high temperature. Tenofovir, an antiretroviral drug with proven activity as a vaginal microbicide, was dispersed in melted Gelucire® (or a mixture of different Gelucire®) to obtain drug-loaded granules. Studies performed on the granules proved that the drug is not altered in the hot-melt granulation process. The granules obtained were included in a matrix formed by the hydrophilic polymers hydroxypropylmethylcellulose and chitosan to obtain vaginal tablets that combine different mechanisms of controlled release: The Gelucire® needs to soften to allow the release of the Tenofovir, and the hydrophilic polymers must form a gel so the drug can diffuse through it. The studies performed with the tablets were swelling behavior, Tenofovir release, and ex vivo mucoadhesion. The tablets containing granules obtained with Tenofovir and Gelucire® 43/01 in a ratio of 1:2 in a matrix formed by hydroxypropylmethylcellulose and chitosan in a ratio of 1.9:1 were selected as the optimal formulation, since they release Tenofovir in a sustained manner over 216h and remain attached to the vaginal mucosa throughout. A weekly administration of these tablets would therefore offer women protection against the sexual transmission of HIV.
Project number: 372
Resiliencia y adaptabilidad en Farmacia: Aprovechamiento de la experiencia de enseñanza-aprendizaje en tiempos de pandemia por CoVid19 aplicando B-Learning y learning analytics
(2022) Notario Pérez, Fernando; Ruiz Caro, Roberto; Veiga Ochoa, María Dolores; Molina Martínez, Irene Teresa; Herrero Vanrell, María del Rocío; Bravo Osuna, Irene; Vicario de la Torre, Marta; Martin Erdocia, Izaskun; Cazorla Luna, Raúl; García Herranz, David; López Cano, José Javier; Martín Illana, Araceli; Gil Alegre, María Esther; Andrés Guerrero, Vanessa; Aragon Navas, Alba
Bigels as drug delivery systems: From their components to their applications
(Drug Discovery Today, 2021) Martín Illana, Araceli; Notario Pérez, Fernando; Cazorla Luna, Raúl; Ruiz Caro, Roberto; Bonferoni, Maria C.; Tamayo, Aitana; Veiga Ochoa, María Dolores
Bigels are systems that usually result from mixing a hydrogel and an organogel: the aqueous phase is commonly formed by a hydrophilic biopolymer, whereas the organic phase comprises a gelled vegetable oil because of the presence of an organogelator. The proportion of the corresponding gelling agent in each phase, the organogel/hydrogel ratio, and the mixing temperature and speed all need to be taken into consideration for bigel manufacturing. Bigels, which are particularly useful drug delivery systems, have already been formulated for transdermal, buccal, and vaginal routes. Mechanical assessments and microscopy are the most reported characterization techniques. As we review here, their composition and unique structure confer promising drug delivery attributes, such as mucoadhesion, the ability to control drug release, and the possibility of including both hydrophilic and lipophilic drugs in the same system.
Vaginal Polyelectrolyte Layer-by-Layer Films Based on Chitosan Derivatives and Eudragit® S100 for pH Responsive Release of Tenofovir
(Marine Drugs, 2020) Cazorla Luna, Raúl; Martín Illana, Araceli; Notario Pérez, Fernando; Bedoya del Olmo, Luis Miguel; Tamayo, Aitana; Ruiz-Caro, Roberto; Rubio, Juan; Veiga Ochoa, María Dolores
Women are still at high risk of contracting the human immunodeficiency virus (HIV) virus due to the lack of protection methods under their control, especially in sub-Saharan countries. Polyelectrolyte multilayer smart vaginal films based on chitosan derivatives (chitosan lactate, chitosan tartate, and chitosan citrate) and Eudragit® S100 were developed for the pH-sensitive release of Tenofovir. Films were characterized through texture analysis and scanning electron microscopy (SEM). Swelling and drug release studies were carried out in simulated vaginal fluid and a mixture of simulated vaginal and seminal fluids. Ex vivo mucoadhesion was evaluated in bovine vaginal mucosa. SEM micrographs revealed the formation of multilayer films. According to texture analysis, chitosan citrate was the most flexible compared to chitosan tartrate and lactate. The swelling studies showed a moderate water uptake (<300% in all cases), leading to the sustained release of Tenofovir in simulated vaginal fluid (up to 120 h), which was accelerated in the simulated fluid mixture (4–6 h). The films had high mucoadhesion in bovine vaginal mucosa. The multilayer films formed by a mixture of chitosan citrate and Eudragit® S100 proved to be the most promising, with zero toxicity, excellent mechanical properties, moderate swelling (<100%), high mucoadhesion capacity, and Tenofovir release of 120 h and 4 h in vaginal fluid and the simulated fluid mixture respectively.
Influence of Chitosan Swelling Behaviour on Controlled Release of Tenofovir from Mucoadhesive Vaginal Systems for Prevention of Sexual Transmission of HIV
(Marine Drugs, 2017) Notario Pérez, Fernando; Martín Illana, Araceli; Cazorla Luna, Raúl; Ruiz Caro, Roberto; Bedoya del Olmo, Luis Miguel; Tamayo, Aitana; Rubio, Juan; Veiga Ochoa, María Dolores
The main challenges facing efforts to prevent the transmission of human immunodeficiency virus (HIV) are the lack of access to sexual education services and sexual violence against young women and girls. Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Vaginal mucoadhesive tablets can be developed by including natural polymers that have good binding capacity with mucosal tissues, such as chitosan or guar gum, semisynthetic polymers such as hydroxypropylmethyl cellulose, or synthetic polymers such as Eudragit® RS. This paper assesses the potential of chitosan for the development of sustained-release vaginal tablets of Tenofovir and compares it with different polymers. The parameters assessed were the permanence time of the bioadhesion—determined ex vivo using bovine vaginal mucosa as substrate—the drug release profiles from the formulation to the medium (simulated vaginal fluid), and swelling profiles in the same medium. Chitosan can be said to allow the manufacture of tablets that remain adhered to the vaginal mucosa and release the drug in a sustained way, with low toxicity and moderate swelling that ensures the comfort of the patient and may be useful for the prevention of sexual transmission of HIV.